Detailed results from the landmark phase III DAPA-HF trial, presented at the ESC Congress 2019, have shown that Dapagliflozin ( Farxiga ), on top of standard of care, has reduced both the incidence of cardiovascular death and the worsening of heart failure.
DAPA-HF is the first outcomes trial with an SGLT2 inhibitor investigating the treatment of heart failure in patients with reduced ejection fraction ( HFrEF ), with and without type-2 diabetes ( T2D).
DAPA-HF trial has met the primary endpoint.
Dapagliflozin has reduced the composite of cardiovascular death or worsening of heart failure by 26% ( p less than 0.0001 ) and showed a reduction in each of the individual components of the composite endpoint.
In analysing each of the components of the primary composite endpoint, there was a 30% decrease ( p less than 0.0001 ) in the risk of experiencing a first episode of worsening heart failure and an 18% decrease ( p=0.0294 ) in the risk of dying from cardiovascular causes.
The effect of Dapagliflozin on the primary composite endpoint was generally consistent across the key subgroups examined.
The trial results have also shown a significant improvement in patient reported outcomes measured by the Kansas City Cardiomyopathy Questionnaire ( KCCQ ) total symptom score and a nominally significant reduction in all-cause mortality by 17% ( 7.9 versus 9.5 patients with an event per 100 patient-years ) in favour of Dapagliflozin.
The safety profile of Dapagliflozin in the DAPA-HF trial was consistent with the well-established safety profile of the medicine.
The proportion of patients with volume depletion ( 7.5% versus 6.8% ) and renal adverse events ( 6.5% vs 7.2% ), which are commonly of concern when treating heart failure, were comparable to placebo.
Major hypoglycaemic events ( 0.2% versus 0.2% ) were rare in both treatment groups.
DAPA-HF ( Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure ) is an international, multi-centre, parallel group, randomised, double-blinded trial in patients with heart failure and reduced ejection fraction ( LVEF less than or equal to 40% ), with and without T2D, designed to evaluate the effect of Dapagliflozin 10mg, compared with placebo, given once daily in addition to standard of care.
The primary composite outcome was time to a worsening heart failure event ( hospitalisation or equivalent event; i.e. an urgent heart failure visit ), or cardiovascular death. ( Xagena )
Source: AstraZeneca, 2019